The health care system is a key channel for delivering interventions to reduce tobacco use, the leading preventable cause of death in the U.S. Much effort has gone into smoking cessation interventions for outpatient practice. Less has been done to target the hospital setting, even though hospitalization may provide a unique opportunity for changing smoking behavior. Hospitalization in today's smoke-free hospitals requires smokers to abstain temporarily from tobacco at the same time that illness may increase their motivation to stop smoking. The candidate's overall research program aims to identify effective smoking cessation interventions for hospitalized patients. Most smokers fail to quit after hospital discharge even with the best intervention (counseling that begins in the hospital and continues by telephone after discharge). More powerful interventions are needed. Adding pharmacotherapy to counseling, which is standard practice in outpatients, has not been tested in this setting. The specific project proposed focuses on smokers hospitalized with myocardial infarction (MI) or unstable angina (UA), for whom smoking cessation is especially valuable and highly cost-effective. Uncertainty about the safety of nicotine replacement in these patients limits its use. A non-nicotine anti-depressant, bupropion, has demonstrated efficacy for smoking cessation and appears to be safe in cardiac patients. It may have the additional benefit of preventing post-MI depression, an independent predictor of mortality. The candidate proposes to test the safety and efficacy of bupropion for smoking cessation in 428 adult smokers hospitalized with MI or UA. A randomized, double-blind, placebo-controlled trial will determine whether bupropion, started in the hospital and continued for 12 weeks, is effective and safe when added to a previously-validated nurse- delivered cognitive-behavioral smoking counseling program. Outcomes will be measured at discharge and 1, 3, and 12 months later. The primary outcome measure is biochemically-confirmed 7- day point prevalence tobacco abstinence at 1 year. Secondary objectives are to determine whether bupropion delays time to relapse; increases end-of-treatment (3-month) smoking cessation rates; reduces depressive symptoms or CHD morbidity; and improves health-related quality of life over 1 year. If found to be safe and effective, bupropion could become a standard element of secondary prevention for patients with acute coronary heart disease, and bupropion or nicotine replacement could be tested in a broader population of hospitalized smokers. The research plan provides ample opportunity for current and future mentees to obtain training in patient-oriented research.